The generation of a high resolution linkage map of the human genome has broad importance for linkage studies, including those involving complex and prevalent genetic conditions, such as heart disease, cancer, arthritis, and Alzheimer's disease. The goal of this proposal is to construct a framework genetic map of human chromosome 9, consisting of a set of index markers whose heterozygosity rate is 70% or better among the polled CEPH/Venezuelan reference pedigrees, with maximum intermarker spacing (sex-averaged) of 5 cM. To achieve this goal, 50 PCR-able polymorphisms of the GTn repeat type will be identified using a cosmid library prepared from a cell line containing chromosome 9 as its sole human component. We have already determined 0 such polymorphisms by this means. STSs not containing repetitive sequence will be determined simultaneously for each new marker. These new polymorphisms, as well as the seven known highly informative polymorphisms on chromosome 9, will be applied to the polled CEPH/Venezuelan pedigrees, with careful attention to error avoidance and detection. Linkage data will be analyzed using LINKAGE and MAPMAKER programs. CHROMLOOK will be used to generate phase and determine cross-overs. Cross-over events between adjacent markers will be directly confirmed. In-situ hybridization will be used to insure correct order of markers and provide a physical correlate to the linkage map. Gaps > 5 cM in the initial map will be filled using in- situ hybridization to guide selection of cosmids for identification of further polymorphisms, and through the use of conventional DNA probes to identify polymorphisms from gap regions.